title: Apoptosis gene polymorphisms and risk of prostate cancer: a hospital-based study of German patients treated with brachytherapy.
abstract: OBJECTIVE
  Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis.
  
  
  METHODS
  Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms.
  
  
  RESULTS
  SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02).
  
  
  CONCLUSIONS
  These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.
authors.affiliation: Clinic of Radiation Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer
authors.forename: Irina
authors.initials: I
authors.lastname: Coinac
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.forename: Nurzhan
authors.initials: N
authors.lastname: Turmanov
authors.forename: Sabine
authors.initials: S
authors.lastname: Haubold
authors.forename: Peter
authors.initials: P
authors.lastname: Schürmann
authors.forename: Florian
authors.initials: F
authors.lastname: Imkamp
authors.forename: Christoph
authors.initials: C
authors.lastname: von Klot
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.forename: Stefan
authors.initials: S
authors.lastname: Machtens
authors.forename: Michael
authors.initials: M
authors.lastname: Bremer
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Johann H
authors.initials: JH
authors.lastname: Karstens
authors.forename: Jürgen
authors.initials: J
authors.lastname: Serth
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001918:Brachytherapy; D016022:Case-Control Studies; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000532:radiotherapy
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor